cas 7298-67-1, N1-(3-ACETYL-4-HYDROXYPHENYL)ACETAMIDE

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Evaluation of in vitro and in vivo anticancer potential of two 5-acetamido chalcones against breast cancer
Two 5’acetamido chalcones, C1 and C2 were synthesized by Claisen-Schmidt condensation method and characterized by IR, LC-MS, 1H NMR and 13C NMR. These compounds were evaluated for anticancer activity in vitro in breast cancer cell lines (MCF-7 and MDA-MB-231) using MTT assay, anti-metastatic assay, apoptotic screening by AO/EB staining and in vivo in N-Methyl-N-nitrosourea (MNU) induced breast carcinoma model. Sprague-Dawley rats with developed tumors (50 mg/kg MNU i.p.) were grouped in four, namely MNU control (0.25 % of CMC p.o.), standard group (doxorubicin 2 mg/kg once in 4 days, i.p.), C1 and C2 groups (50 mg/kg p.o. each). After 21 days of treatments, tumor volume and weight were assessed. Excised tumors were subjected to DNA fragmentation study. MTT assay showed IC50 values of 62.56 and 37.8 μM by for C1 and C2. Both compounds increased apoptotic bodies more than 3 fold compared to normal control in AO/EB staining. Antimetastatic (scratch wound) assay showed a significant (p0.05) reduction in cell migration after 24 h and 48 h treatments compared to normal control. In in vivo studies, tumor weight and tumor volume were significantly (p0.05) reduced in the doxorubicin group as well as in test groups compared to MNU control. DNA fragmentation assay showed an increase in the number of bands formed in C1 and C2 compared to normal control. Results obtained from in vitro and in vivo studies demonstrated the significant anticancer potentials of C1 and C2.
Wankhede, Sonal,Kumar, Nitesh,Simon, Lalitha,Biswas, Subhankar,Gourishetti, Karthik,Ramalingayya, Grandhi Venkata,Joshi, Mit,Rao, C. Mallikarjuna
p. 1150 - 1163
(2017)
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Method for diacetate intermediate 5 - acetamide group -2 - (2, 3 - epoxypropoxy) acetophenone
The invention belongs to the field of organic photochemical and drug intermediate chemistry. The invention particularly relates to a method for synthesizing diacetate intermediate - acetamide group 5 - (-2 - 2 epoxypropoxy) acetophenone containing acetylated 3 - photochemical rearrangement reaction in series. The reactant is cooled to the polar organic solvent, Fries rearrangement is carried out directly by ultraviolet - visible light irradiation with specific wavelength, and the intermediate Fries acetyl 2 -4 - acetyl aminophenol is obtained by heating and evaporating the solvent after the reaction is finished. Sodium hydroxide was added to prepare the phenol salt. Then, an intermediate 5 - acetamide group -2 - (2, 3 - epoxypropoxy) acetophenone was obtained by reaction with epichlorohydrin. The tandem type synthesis method disclosed by the invention is simple and feasible, and low-toxicity, high-efficiency and cheap green chemical reagents are used in the synthesis process.
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Paragraph 0022; 0026-0027; 0029-0030; 0032-0033; 0035-0036..

(2021/11/14)

Redox-Neutral Selenium-Catalysed Isomerisation of para-Hydroxamic Acids into para-Aminophenols
A selenium-catalysed para-hydroxylation of N-aryl-hydroxamic acids is reported. Mechanistically, the reaction comprises an N?O bond cleavage and consecutive selenium-induced [2,3]-rearrangement to deliver para-hydroxyaniline derivatives. The mechanism is studied through both 18O-crossover experiments as well as quantum chemical calculations. This redox-neutral transformation provides an unconventional synthetic approach to para-aminophenols.
Chuang, Hsiang-Yu,Schupp, Manuel,Meyrelles, Ricardo,Maryasin, Boris,Maulide, Nuno
p. 13778 - 13782
(2021/03/31)

Click chemistry synthesis, biological evaluation and docking study of some novel 2′-hydroxychalcone-triazole hybrids as potent anti-inflammatory agents
A hybrid pharmacophore approach is used to design and synthesize two novel series of 2′-hydroxychalcone-triazole hybrid molecules 6a-j and 8a-j. These compounds were fully characterized by spectral and elemental analyses. They were evaluated in vitro and in vivo for anti-inflammatory activity. Most of compounds were selective inhibitors for COX-2. Among them, compounds 6d, 6f, 6i, 8c, 8e and 8h demonstrated highly potent dual inhibition of COX-2 (IC50 = 0.037–0.041 μM) and 15-LOX (IC50 = 1.41–1.80 μM). Compounds 6i, 8c and 8h showed 116%, 113% and 109% of the in vivo anti-inflammatory activity of celecoxib. Therefore, compounds 6d, 6f, 6i, 8c, 8e and 8h-j are potent dual inhibitors of COX-2 and 15-LOX. Docking study over COX-2 and 15-LOX active sites ensures the binding affinity and selectivity. These compounds are promising candidates for further development as anti-inflammatory drugs.
Abdu-Allah, Hajjaj H. M.,Boshra, Andrew N.,Hayallah, Alaa M.,Mohammed, Anber F.
(2020/01/06)

AHR INHIBITORS AND USES THEREOF
The present invention provides compounds useful as inhibitors of AHR, compositions thereof, and methods of using the same.
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Paragraph 0362; 0363; 0366; 0367

(2019/03/02)

Total Synthesis of Fontanesine B and Its Isomer: Their Antiproliferative Activity against Human Colorectal Cancer Cells
A concise synthesis of pyrano[3,2-e]indole alkaloid fontanesine B by a Fischer indolization is described. This key Fischer indolization starts with the pyran-ring and alkene intact, facilitating potential synthetic applications. Furthermore, fontanesine B and its isomer were evaluated for in vitro antiproliferative activity against human colorectal cancer cells. The isomer of fontanesine B showed higher antiproliferative activity than the natural product, fontanesine B (2).
Abe, Takumi,Itoh, Tomoki,Terasaki, Masaru
(2019/07/10)

Benzo heterocyclic derivatives, their preparation and their use in medicine (by machine translation)
The present invention relates to benzo heterocyclic derivatives, their preparation and their use in medicine. In particular, the invention relates to a general formula (I) indicated by the compound, the compound has anti-tumor of the use, the inhibition of angiogenesis and as the role of the HIF - 1 α inhibitors in the medical application. Wherein the general formula (I) of each substituent in the definition in the description of the same. (by machine translation)
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Page/Page column 20; 21; 22

(2018/09/21)

Design, synthesis, and evaluation of benzofuran derivatives as novel anti-pancreatic carcinoma agents via interfering the hypoxia environment by targeting HIF-1α pathway
Pancreatic ductal adenocarcinoma (PDAC) is one of the most common type of pancreatic cancer, and has still been the medicinal mystery. New drugs and treatment strategies are urgently needed. In this study, 32 benzofuran derivatives are designed, synthesized and evaluated as potential agents against the pancreatic cancer. Among them, compound 9o with the best physicochemical and pharmacokinetic properties exhibited excellent cytotoxicity against many tumor cell lines. In vivo study showed that compound 9o dramatically suppressed the tumor growth of nude mice. Furthermore, compound 9o could affect the hypoxia environment through Hif-1α/VEGF pathway, resulting in the anti-angiogenic activity. These studies indicated that compound 9o was a promising candidate for the treatment of PDAC, deserving further studies.
Xu, Xiao-li,Yang, Ying-rui,Mo, Xiao-fei,Wei, Jin-lian,Zhang, Xiao-jin,You, Qi-dong
p. 45 - 62
(2017/05/31)

Synthesis and evaluation of N-(benzofuran-5-yl)aromaticsulfonamide derivatives as novel HIF-1 inhibitors that possess anti-angiogenic potential
Hypoxia-inducible factor-1 (HIF-1) as a key mediator in tumor metastasis, angiogenesis, and poor patient prognosis has been recognized as an important cancer drug target. A novel series of N-(benzofuran-5-yl)aromaticsulfonamide derivatives were synthesized and evaluated as HIF-1 inhibitor. Among these compounds, 7q exhibited specific inhibitory effects on HIF-1 by downregulating the expression of HIF-1α under hypoxic conditions. It inhibited the HIF-1 transcriptional activity (IC50?=?12.5?±?0.7?μM) and secretion of VEGF (IC50?=?18.8?μM) in MCF-7 cells. Meanwhile, it also significantly suppressed hypoxia-induced migration of HUVEC cells in nontoxic concentrations. Additionally, tube formation assay demonstrated its anti-angiogenesis activity. Finally, the in vivo study indicated that compound 7q could retard angiogenesis in CAM model. These findings supported the HIF-1 inhibitory effect and anti-angiogenic potential of this class of compounds as HIF-1 inhibitor.
Wei, Jinlian,Yang, Yingrui,Li, Yali,Mo, Xiaofei,Guo, Xiaoke,Zhang, Xiaojin,Xu, Xiaoli,Jiang, Zhengyu,You, Qidong
p. 1737 - 1746
(2017/03/08)

Synthesis and antiproliferative activity of new 1,2,3-triazole/flavone hybrid heterocycles against human cancer cell lines
A series of new 1,2,3-triazole/flavone hybrid heterocycles were synthesized from 6-amino flavone via key intermediate N-propargyl flavone 6 by adopting the Sharpless Click reaction. Copper(I) catalyzed 1,3-dipolar cycloaddition reaction that gave products in high yields. All the synthesized compounds were screened for their in vitro antiproliferative activity against four human cancer cell lines, HeLa (cervical cancer cell line), MIA PaCa (pancreatic cancer cell line), MDA-MB-231 (breast cancer cell line), and IMR 32 (neuroblastoma cancer cell line). Compounds 7a, 7b, 7d, 7g (GI50 = 0.01–0.68 μM) demonstrated promising antiproliferative activity.
Sowjanya,Jayaprakash Rao,Murthy
p. 1864 - 1871
(2017/09/25)

COMPOUNDS FOR THE TREATMENT OF AMYLOID-ASSOCIATED DISEASES
This invention provides novel compounds of formulae (I) or (II) or a stereoisomer, enantiomer, racemic, or tautomer thereof, (I) (II) wherein the substituents are as defined in the specification. The present invention also relates to the novel compounds for use as a medicine, more in particular for the prevention or treatment of amyloid-related diseases, more specifically certain neurological disorders, such as disorders collectively known as tauopathies, disorders characterized by cytotoxic α-synuclein amyloidogenesis. The present invention also relates to the use of said novel compounds for the manufacture of medicaments useful for treating such amyloid-related diseases. The present invention further relates to pharmaceutical compositions including said novel compounds and to methods for the preparation of said novel compounds.
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Page/Page column 163

(2016/06/14)

Compound and application of compound in preparation of medicines
The invention discloses a compound and its application in a medicine. the invention specifically provides a compound as shown in the formula (I) or a stereisomer, a geometrical isomer, a tautomer, a racemate, nitric oxide, hydrate, a solvate, a metabolite, pharmaceutically acceptable salts or a prodrug of the compound as shown in the formula (I). The invention also discloses an application of the compound in preparation of a medicine. The medicine is used in treating cancers.
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Paragraph 0150; 0151; 0152; 0285

(2016/10/08)

Selected novel 5’-amino-2’-hydroxy-1, 3-diaryl-2- propen-1-ones arrest cell cycle of HCT-116 in G0/G1 phase
A series of 5’-amino-2’-hydroxy-1,3-diaryl-2-propen-1-ones (AC1-AC15) were synthesized by Claisen-Schmidt condensation of 5'-acetamido-2’-hydroxy acetophenone with various substituted aromatic aldehydes. The syn- thesized compounds were characterized by FTIR, 1H NMR and mass spectrometry and evaluated for their selec- tive cytotoxicity using MTT assay on two cancer cell lines namely breast cancer cell line (MCF-7), colon cancer cell line (HCT-116) and one normal kidney epithelial cell line (Vero). Among the tested compounds, AC-10 showed maximum cytotoxic effect on MCF-7 cell line with IC50 value 74.7 ± 3.5 μM. On HCT-116 cells, AC-13 exhibited maximum cytotoxicity with IC50 value 42.1 ± 4.0 μM followed by AC-14 and AC-10 with IC50 values 62 ± 2.3 μM and 95.4 ± 1.7 μM respectively. All tested compounds were found to be safe on Vero cell line with IC50 value more than 200 μM. Based on their highest efficacy on HCT-116, AC-10, AC-13 and AC-14 were selected for mechanistic study on this cell line by evaluating changes nucleomorphological characteristics using acridine orange-ethidium bromide (AOEB) dual stain and by analyzing cell cycle with flow cytometry using propidium iodide stain. In AOEB staining, all three tested compounds showed significant (p 0/G1 phase and by AC-13 in G0/G1 and G2/M phase. The study reflected the potential of AC-10, AC-13 and AC-14 to be the lead molecules for further optimization.
Simon, Lalitha,Srinivasan,Kumar, Nitesh,Reddy, Neetinkumar D,Biswas, Subhankar,Mallikarjuna Rao,Moorkoth, Sudheer
p. 21 - 32
(2016/01/30)

Synthesis and anti-cancer activity of novel thiazolidinone analogs of 6-aminoflavone
Novel heterocyclic analogs were synthesized by combining a flavone nucleus and thiazolidinone ring in an effort to potentiate the existing anti-cancer activity of flavone. The syntheses of 6-aminoflavone, 6-amino-3-methoxyflavone, 6-amino-3-methoxy-3',4'-dimethxyflavone and their corresponding thiazolidinone analogs were performed. Fifteen novel analogs were synthesized and evaluated for their anti-cancer activity using cell-based assay techniques and in vivo testing. As expected, the analogs improved cytotoxicity and were shown to increase the life span of cancer-bearing mice. Cytotoxicity was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays in HeLa, MDA-MB-435, and Vero cell lines. In vivo evaluation of anti-cancer activity performed in albino mice bearing Dalton's ascites carcinoma showed that the new analogs enhanced life span and prevented increases in body weight owing to tumor volumes. Moreover, cell-cycle analysis and Hoechst staining analysis proved the apoptotic potential of these analogs. Preliminary pharmacokinetic evaluation was carried out on the synthesized compounds to determine the lipophilicity and pKa. Lipophilicity was determined using high-performance liquid chromatography and the results showed a direct correlation between the observed anti-cancer activity and log P value, while pKa values indicated the ionizing range which is a prediction tool for solubility and permeability.
Moorkoth, Sudheer
p. 974 - 985
(2016/02/03)

Influence of the alkylsulfonylamino substituent located at the 6-position of 2,2-dimethylchromans structurally related to cromakalim: From potassium channel openers to calcium entry blockers?
The present study described the synthesis of original R/S-6- alkylsulfonylamino-3,4-dihydro-2,2-dimethyl-2H-1-benzopyrans bearing a 3- or 4-substituted phenylthiourea or phenylurea moiety at the 4-position. Their biological effects were evaluated both on insulin-secreting and smooth muscle cells and were compared to those of reference KATP channel activators such as (±)-cromakalim, diazoxide and previously synthesized cromakalim analogues. The study aimed at exploring the influence of the introduction of an alkylsulfonylamino substituent at the 6-position of 2,2-dimethylchromans in order to improve biological activity, tissue selectivity but also hydrophilicity of dihydrobenzopyran derivatives. Several compounds were found to be equipotent or even more potent than (±)-cromakalim and diazoxide at inhibiting the insulin releasing process. Most of the newly synthesized and more hydrophilic dihydrobenzopyrans also exhibited a marked vasorelaxant activity although they were less potent than (±)-cromakalim. Additional pharmacological and radioisotopic investigations suggested that R/S-N-3-chlorophenyl-N-(3,4-dihydro- 6-methylsulfonylamino-2,2-dimethyl-2H-1-benzopyran-4-yl)thiourea (21) did not act as a potassium channel opener but rather as a Ca2+ entry blocker.
Florence, Xavier,Desvaux, Vincent,Goffin, Eric,De Tullio, Pascal,Pirotte, Bernard,Lebrun, Philippe
p. 36 - 46
(2014/05/06)

Synthesis and evaluation of a series of novel imidazolidinone analogues of 6-aminoflavone as anticancer and anti-inflammatory agents
The flavone moiety is a potential pharmacophore known for its diverse range of pharmacological activities. Aminoflavones have recently been the subject of considerable attention as lead molecules in several cancer research projects. Imidazolidinone heterocycles represent another biologically active scaffold with known cytotoxic properties. In an attempt to provide synergistic cytotoxic activity, these two moieties have been combined, and the resulting novel analogues evaluated for their anticancer and anti-inflammatory activities. The results revealed that the cytotoxicities of these compounds were fivefold greater than those of aminoflavone. DNA histograms obtained from cell cycle analysis in the presence of these compounds were apoptotic in their nature. Furthermore, the in vivo screening of these compounds using Ehrlich's ascites tumour model showed an increase in life span, whereas an in vivo anti-inflammatory study resulted in the enhancement of the anti-inflammatory potential. The results therefore supported the hypothesis that there is a relationship between inflammation and cancer.
Moorkoth, Sudheer,Srinivasan,Gopalan Kutty,Joseph, Alex,Naseer
p. 5066 - 5075
(2013/09/23)

DIHYDROBENZOPYRAN, THIOCHROMAN, TETRAHYDROQUINOLEINE AND TETRAHYDRONAPHTALENE DERIVATIVES AND THEIR USE IN ANTICANCER THERAPY
New dihydrobenzopyran, thiochroman, tetrahydroquinoleine and tetrahydronaphthalene derivatives and their use in anti-cancer therapy with the general formula (I).
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Page/Page column 29

(2012/08/28)

Dihydrobenzopyran, thiochroman, tetrahydroquinoleine and tetrahydronaphthalene derivatives and their use in anti-cancer therapy
New dihydrobenzopyran, thiochroman, tetrahydroquinoleine and tetrahydronaphthalene derivatives and their use in anti-cancer therapy with the general formula :
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(2012/08/28)

Modulation of the 6-position of benzopyran derivatives and inhibitory effects on the insulin releasing process
The synthesis of different series of 4- and 6-substituted R/S-3,4-dihydro-2,2-dimethyl-2H-1-benzopyrans is described. All of these new benzopyran derivatives were bearing, at the 4-position, a phenylthiourea moiety substituted on the phenyl ring by a meta or a para-electron-withdrawing group such as Cl or CN. The study aimed at exploring the influence of the nature of the substituent at the 6-position in order to develop new benzopyran-type K ATP channel activators exhibiting an improved selectivity towards the insulin secreting cells. The original compounds were examined in vitro on rat pancreatic islets (inhibition of insulin release) as well as on rat aorta rings (vasorelaxant effect) and their activity was compared to that of the reference KATP channel activators (±)-cromakalim, (±)-pinacidil, diazoxide and to previously synthesized cromakalim analogues. Structure-activity relationships indicated that the inhibitory effect on the insulin secreting cells was related to the lipophilicity of the molecules and to the size of the substituent located at the 6-position. A marked inhibitory activity on the insulin secretory process was obtained with molecules bearing a bulky tert-butyloxycarbonylamino group at the 6-position (20-23). The latter compounds were found to have the same efficacy on the pancreatic endocrine tissue than some previously described molecules. Lastly, radioisotopic experiments further identified R/S-N-4-chlorophenyl-N′-(6-tert-butyloxycarbonylamino-3,4- dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)thiourea (23) as a KATP channel opener.
Florence, Xavier,Dilly, Sébastien,De Tullio, Pascal,Pirotte, Bernard,Lebrun, Philippe
experimental part
p. 3919 - 3928
(2011/08/06)

Synthesis, antiproliferative activities and in vitro biological evaluation of novel benzofuransulfonamide derivatives
In a cell-based screen of novel antiproliferative agents, the hit compound 1a, which bears a benzofuransulfonamide scaffold, exhibited broad-spectrum antiproliferative activities against a panel of tumor cell lines. The promising in vitro antiproliferative activity and structural novelty of 1a prompted us to investigate the synthesis of five analogs of 1a and test their antiproliferative activities. The most potent analogue, 1h, exhibited enhanced antiproliferative activities compared with the parent 1a, and exhibited an IC50 value against NCI-H460 cells of 4.13 μM compared with 4.52 μM for the positive control cisplatin. Flow cytometric analysis revealed that 1h induces significant levels of apoptosis in NCI-H460 cells in vitro at low micromolar concentrations. These results suggest that 1a and analogs based on its benzofuransulfonamide scaffold may constitute a novel class of antiproliferative agents, which deserve further study.
Yang, Li,Lei, Hua,Mi, Cheng-Gen,Liu, Huan,Zhou, Tian,Zhao, Ying-Lan,Lai, Xiao-Yun,Li, Zi-Cheng,Song, Hang,Huang, Wen-Cai
scheme or table
p. 5389 - 5392
(2011/10/12)

Flavonols
A compound of the formula (I): wherein R is selected from the group consisting of H, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl and acyl, each of which may be optionally substituted;R1 is an organic moiety that is capable of being converted into a charged group;each X and Y is independently selected from the group consisting of H, halogen, —CN, —NO2, —CF3, —OCF3, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, heteroalkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, heteroarylalkyl, arylalkenyl, cycloalkylheteroalkyl, arylheteroalkyl, heterocycloalkylheteroalkyl, heteroarylheteroalkyl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, alkoxyaryl, alkenyloxy, alkynyloxy, cycloalkyloxy, heterocycloalkyloxy, aryloxy, heteroaryloxy, arylalkyloxy, phenoxy, benzyloxy, amino, alkylamino, aminoalkyl, acylamino, arylamino, sulfonylamino, sulfinylamino, —COOH, —COR2, —COOR2, —CONHR2, —NHCOR2, —NHCOOR2, —NHCONHR2, C(═NOH)R2, alkoxycarbonyl, alkylaminocarbonyl, sulfonyl, alkylsulfonyl, alkylsulfinyl, arylsulfonyl, arylsulfinyl, aminosulfonyl, SR2 and acyl, each of which may be optionally substituted;each R2 is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, heteroarylalkyl, and acyl, each of which may be optionally substituted;m is an integer selected from the group consisting of 0, 1, 2, 3, 4 and 5;p is an integer selected from 0, 1, 2 and 3; or a pharmaceutically acceptable salt or prodrug thereof.
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Page/Page column 17; 23

(2011/01/12)

N-sulfamoyl-N'-benzopyranpiperidine compounds and uses thereof
N-sulfamoyl-N′-benzopyranpiperidine compounds of formula I and their physiologically acceptable acid addition salts, pharmaceutical compositions comprising them, processes for their preparation, and their use for the treatment and/or inhibition of glaucoma, epilepsy, bipolar disorders, migraine, neuropathic pain, obesity, type II diabetes, metabolic syndrome, alcohol dependence, and/or cancer, and related concomitant and/or secondary diseases or conditions.
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Page/Page column 7; 8

(2008/06/13)

N-SULFAMOYL-N’-BENZOPYRANPIPERIDINES AS INHBITORS OF CARBONIC ANHYDRASES
The present invention relates to novel N-sulfamoyl-N'-benzopyranpiperidines of general formula (I) and their physiologically acceptable acid addition salts, to pharmaceutical compositions comprising them, processes for their preparation, and their use for the prophylaxis and/or treatment and/or prevention and/or inhibition of glaucoma, epilepsy, bipolar disorders, migraine, neuropathic pain, obesity, type II diabetes, metabolic syndrome, alcohol dependence, and/or cancer, and its concomitant and/or secondary diseases or conditions.
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Page/Page column 14; 16

(2008/06/13)

SPIROCHROMANONE DERIVATIVES AS ACETYL COENZYME A CARBOXYLASE (ACC) INHIBITORS
The invention relates to a compound of a formula (I): , or a pharmaceutically acceptable salt or ester thereof, useful as a therapeutic agent for various ACC-related disorders.
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Page/Page column 90-91

(2008/06/13)

QSAR studies of paeonol analogues for inhibition of platelet aggregation
Various paeonol analogues were synthesized and tested in vitro as inhibitors of platelet aggregation. Structural properties (or descriptors) of paeonol analogues were calculated and the structure-activity relationships were determined. Several multiple linear and nonlinear regression models and back-propagation neural network model were tested and the latter using relative positive charge, hydration energy, and hydrophilic factor as inputs gave the best data fitting with R2 = 0.89 and qpre2=0.66. The correlation coefficient between antiplatelet inhibition activity with an interaction energy between the paeonol compounds with COX-1 enzyme is only 0.39.
Doble, Mukesh,Karthikeyan,Padmaswar,Akamanchi
p. 5996 - 6001
(2007/10/03)

Potential therapeutic antioxidants that combine the radical scavenging ability of myricetin and the lipophilic chain of vitamin E to effectively inhibit microsomal lipid peroxidation
The flavonol myricetin, reacts with oxygen-centred galvinoxyl radicals 28 times faster than d-α-tocopherol (vitamin E), the main lipid-soluble antioxidant in biological membranes. Moreover, each myricetin molecule reduces twice as many such radicals as vitamin E. However, myricetin fails to protect vitamin E-deficient microsomes from lipid peroxidation as assessed by the formation of thiobarbituric acid reactive substances (TBARS). Novel and potentially therapeutic antioxidants have been prepared that combine the radical-scavenging ability of a myricetin-like head group with a lipophilic chain similar to that of vitamin E. C6-C12 alkyl chains are attached to the A-ring of either a 3,3′,4 ′,5′-tetrahydroxyflavone or a 3,2 ′,4′,5′-tetrahydroxyflavone head group to give lipophilic flavonoids (ClogP=4 to 10) that markedly inhibit iron-ADP catalysed oxidation of microsomal preparations. Orientation of the head group as well as total lipophilicity are important determinants of antioxidant efficacy. MM2 models indicate that our best straight chain 7-alkylflavonoids embed to the same depth in the membrane as vitamin E. The flavonoid head groups are prepared by aldol condensation followed by Algar-Flynn-Oyamada (AFO) oxidation or by Baker-Venkataraman rearrangement. The alkyl tails are introduced by Suzuki or Negishi palladium-catalysed cross-coupling or by cross-metathesis catalysed by first generation Grubbs catalyst, which tolerate phenolic hydroxyl and ketone groups.
Bennett, Christopher J.,Caldwell, Stuart T.,McPhail, Donald B.,Morrice, Philip C.,Duthie, Garry G.,Hartley, Richard C.
p. 2079 - 2098
(2007/10/03)

FLAVONOID COMPOUNDS AS THERAPEUTIC ANTIOXIDANTS
Novel flavonoid compounds having anti-oxidant activity are described. The compounds have been shown to exhibit anti-oxidative properties in biological systems and their utility in a sunscreen or skincare composition or to treat conditions involving oxidative damage, especially curative or prophylactic treatment of Alzheimer's disease or ischaemia-reperfusion injury, is described.
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Page 72-73

(2008/06/13)

One-step reaction of friedel-crafts acylation and demethylation of aryl-methyl ethers catalyzed by ytterbium(III) triflate
Catalytic amount of ytterbium(III) inflate [Yb(OTf)3] has been used to catalyze Friedel-Crafts acylation and demethylation of aryl-methyl ethers in one-step reaction to produce hydroxyacylphenones with moderate yields under mild conditions.
Su, Weike,Jin, Can
p. 4199 - 4205
(2007/10/03)

Fries-type rearrangement of acylanilides in the presence of ytterbium triflate
Ytterbium triflate has been used to catalyse the Fries-type rearrangement of various acylanilides with moderate yields when lithium perchlorate was used as co-catalyst.
Su, Weike,Jin, Can
p. 611 - 613
(2007/10/03)

Cdk inhibitors having 3-hydroxychromen-4-one structure
The present invention relates to a novel 3-hydroxychromen-4-one derivative of formula (1), pharmaceutically acceptable salt, hydrate, solvate or isomer thereof which is useful as an inhibitor for Cyclin Dependent Kinase (“CDK”); to a process for preparing the compound of formula (1); and to a composition for suppression or treatment of cancer and diseases induced by cell proliferation such as inflammation, angiostenosis, angiogenesis, etc. comprising the compound of formula (1) as an active component together with pharmaceutically acceptable carriers.
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(2008/06/13)

Synthesis and pharmacological evaluation of K(ATP)-channel openers related to cromakalim: Introduction of arylsulphonylurea moieties
A series of 4-(arylsulphonylaminocarbonylamino)-3,4-dihydro-2,2-dimethyl-2 H-1-benzopyran derivatives were prepared and evaluated as potential ATP-sensitive potassium-channel activators. Pharmacological studies showed that some compounds expressed vasodilator efficacy on vascular smooth muscle. The compounds had no inhibitory activity on insulin secretion from pancreatic β-cells.
Khelili,Nguyen,Lebrun,Delarge,Pirotte
p. 189 - 193
(2007/10/03)

Synthesis and in-vitro evaluation of platelet aggregation inhibitory activity of paeonol and its analogues
Paeonol (1-(2-hydroxy-4-methoxyphenyl)ethanone) and a series of substituted 1-(2-hydroxyphenyl)ethanone derivatives were synthesized and screened as inhibitors of platelet aggregation. The compounds with the greatest anti-platelet potential among the series tested were 1-(2,5-dihydroxyphenyl)ethanone (65.36% inhibition at 300 μM against 5 μM ADP), paeonol(36.31%), 1-(2-hydroxy-5-methoxyphenyl)ethanone (24.47%), 1-(2-hydroxy-5-nitrophenyl) ethanone (30.40%) and 1-(5-chloro-2-hydroxy-4-methylphenyl)ethanone (24.43%).
Akamanchi,Padmawar,Thatte,Rege,Dahanukar
p. 323 - 329
(2007/10/03)

4-oxospiro[benzopyran-2,4'-piperidines] as selective α(1a)-adrenergic receptor antagonists
The 4-oxospiro[benzopyran-2,4'-piperidine] ring system is contained within potent class III antiarrhythmic agents. We highlight how these agents can be chemically transformed into a new class of potent (25-fold) α(1a)-receptor subtype adrenergic antagonists.
Nerenberg, Jennie B.,Erb, Jill M.,Bergman, Jeffrey M.,O'Malley, Stacey,Chang, Raymond S. L.,Scott, Ann L.,Broten, Theodore P.,Bock, Mark G.
p. 291 - 294
(2007/10/03)

Asymmetric Synthesis of MK-0499
Described herein is an efficient asymmetric synthesis of the potent antiarrhthymia agent MK-0499.The route is convergent and is highlighted by two stereoselective reactions.A ruthenium-catalyzed, enantioselective hydrogenation of an enamide was developed for the preparation of the key amine intermediate.Oxazaborolidine-mediated ketone reduction was utilized to establish the alcohol stereochemistry.Optimization of this chemistry led to an IPA modified reduction method which provides enhanced stereoselectivity.
Tschaen, David M.,Abramson, Lee,Cai, Dongwei,Desmond, Richard,Dolling, Ulf-H.,et al.
p. 4324 - 4330
(2007/10/02)

Synthesis and Biochemical Evaluation of a Series of Aminoflavones as Potential Inhibitors of Protein-Tyrosine Kinases p56lek, EGFr, and p60v-src
A series of nitroflavones, 8a-p, and their corresponding aminoflavone hydrochloride salts, 10a-p, was synthesized.The preparation of nitroflavones 8b-i,o,p began with commercially available o-hydroxyacetophenones 2b-f which were converted to o-hydroxynitroacetophenones 3a-h via a variety of nitration methods, followed by condensation with nitrobenzyl chlorides and cyclization under acidic condition.The nitroflavones 8a,j-n were prepared by nitration of the corresponding flavones 7a-e.These new compounds were evaluated for their abilities to inhibit the in vitro protein-tyrosine kinase activities of p56lek, EGFr, and p60v-src, and all of the active compounds were amino-substituted flavones.None of the nitroflavones inhibited the enzymes.The most active substance in this series against p56lek was compound 10j, which had an IC50 of 18 μM.When tested versus EGFr, compounds 10a,m displayed IC50's of 8.7 and 7.8 μM, respectively.Against p60v-src, 10a,m showed IC50 values of 28.8 and 38.4 μM, respectively.
Cushman, Mark,Zhu, Helen,Geahlen, Robert L.,Kraker, Alan J.
p. 3353 - 3362
(2007/10/02)

4-Oxospiro[benzopyran-2,4'-piperidines] as class III antiarrhythmic agents. Pharmacological studies on 3,4-dihydro-1'-[2-(benzofurazan-5-yl)- ethyl]-6-methanesulfonamidospiro[(2H)-1-benzopyran-2,4'-piperidin]-4-one (L- 691,121) [2]
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Elliott,Selnick,Claremon,Baldwin,Buhrow,Butcher,Habecker,King,Lynch Jr.,Phillips,Ponticello,Radzilowski,Remy,Stein,White,Young
p. 3973 - 3976
(2007/10/02)

Synthesis and structure-activity relationships of new β-adrenoreceptor antagonists. Evidence for the electrostatic requirements for β-adrenoreceptor antagonists
A series of mono- and disubstituted phenoxypropanolamines, structurally related to practolol and acebutolol, has been synthesized and tested for β-adrenoreceptor blocking activity. Structure-activity relationships are discussed. The reasons for the lack of activity of compounds 3n and 4n have also been examined. The results suggest that the negative electrostatic potential above the phenyl ring of phenoxypropanolamines is essential for binding activity and point to the presence of an electropositive residue in the β-adrenoreceptor binding site.
Kettmann,Csollei,Racanska,Svec
p. 843 - 851
(2007/10/02)